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01 Dec 2013

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Your Own Medicine

Three years ago, Gene Williams (MBA 1987) helped two parents set up a drug company to save their son's life. Their new patient-driven drug development blueprint may just end up saving the pharmaceutical industry too.

CHARLEY SECKLER in the midst of the first-ever trial for a DMD treatment at Johns Hopkins University.

Photo courtesy the Seckler Family

by Dan Morrell

There's this picture of Charley Seckler from last summer that his mom has sent to everyone: Her 12-year-old son, sitting cross-legged on a hospital bed in jeans and Chuck Taylors, mussed brown hair, smiling just enough to reveal dimples, with his hand out in front of him, holding two small white pills.

"First dose of HT-100. That's it," she says, pulling up the photo on the computer at her office in Great Barrington, Massachusetts. The space—a loft, shared with a home-and-clothing shop—is the headquarters of Charley's Fund, a nonprofit that Tracy Seckler and her husband, Benjy, founded in 2004 after their son, then three years old, was diagnosed with Duchenne muscular dystrophy (DMD).

The pills in Charley's hand are the first drug he has ever taken that directly targets his DMD, a rare degenerative disorder in boys that weakens the body's muscles, usually putting sufferers in wheelchairs in adolescence and shutting down their heart and lungs in their 20s.

For years, the drug—which could possibly both halt muscle damage and help build new muscle—had been one of several potential treatments the Secklers chased to no avail, often stuck following promising science to dead ends. That changed three years ago, when former pharmaceutical executive Gene Williams (MBA 1987) pitched a new vision to the couple: Charley's disease is progressing daily. You can't settle for the typical schedule of drug discovery and development.

So forget the drug companies. We'll form our own.

“Well, you can't just tell me that at nine o'clock at night and think I'm going to go to sleep. You've got to tell me what it is." It's early July 2004, and Charley's pediatrician wants Tracy to come in to see her the next morning. Some of Charley's test results had just been faxed over from the neurologist, and they don't look normal. Tracy won't let her get off the phone. "No, you've got to tell me what you think it is." The doctor relents: The level of creatine kinase—an enzyme indicative of muscle damage—in a normal person's blood is around 50 units per liter, maybe as high as 100 after a workout. Charley's was 20,000. It suggested muscular dystrophy.

With everyone else in the house asleep, Tracy spent all night online. She found pictures of children with muscular dystrophy employing something called the Gowers' sign to get off the floor, using their hands to push themselves up. Just like Charley, she thought. And those high levels of creatine kinase, she found, likely pointed to DMD, the most common form of muscular dystrophy. By morning, she had made her own diagnosis; later that morning, the doctors confirmed it.

Tracy didn't tell Benjy about the pediatrician's call and her online diagnosis that morning, though. She wanted him to have one last morning of kissing his three kids goodbye and going to work and thinking everything was OK. One final bit of normal, she thought.

The initial post-diagnosis plan was for Benjy to continue his busy schedule as a radiologist, and for Tracy to quit teaching so she could take Charley to doctors' appointments. After a few months of visits to top specialists, they realized there was no point. There was nothing the doctors could do for Charley. By November, the Secklers had set up Charley's Fund, with Tracy running it full-time.

“Is your son on any treatment that is a direct result of what you have done?" Williams asked. "No," admitted Tracy. "I'm going to change that," he said.

In its first few years, the fund concentrated on raising money to support research, even hiring a research director to keep tabs on their investments. At night, the couple would scour medical journals, searching for new leads. In 2008, Benjy came across an article on halofuginone (HT-100), a drug compound derived from an ancient Chinese herb that had shown promising results in treating muscular dystrophy in mice. They tracked it down to an Israeli biotech but hit a wall. VC backers had spent $80 million to have the biotech develop it as a potential cancer drug, eventually giving up when even low doses resulted in severe nausea during clinical trials. Still, the drug became a focal point for the Secklers. "Here was this drug that showed promise," says Tracy. "It's sitting on the shelf, and it's not going anywhere. What are we doing wrong?"

Frustrated, they hit up their network, looking for some way to put these kinds of potential cures into motion. "If you are trying to do something innovative in biotech, the person you need to speak to is Gene Williams," one of Tracy's contacts told her. The first conversation wasn't promising: The Secklers came in planning to set up a venture fund to support companies pursuing DMD treatments and were looking for a fund manager; Williams, a former SVP at Genzyme with no fund-managing experience, said he was not the guy for them. But he was interested in what they were doing and wanted to stay in touch.

In subsequent conversations in the spring of 2010, the Secklers told Williams about HT-100. Williams went to work, offering the venture capital group that held the compound a deal that would allow him and the Secklers to purchase it for the relatively low price of $1.1 million, develop it specifically for DMD, and let the VC investors reap the rewards when and if the drug was successfully commercialized. To make that happen, Williams said, the Secklers would have to shift from just finding and funding science to becoming an actual pharmaceutical company, developing their own drugs. His offer was simple. "Is your son on any treatment that is a direct result of what you have done?" he asked. "No," admitted Tracy. "I'm going to change that," Williams said. DART (Disease Action Research Therapy) Therapeutics was born in the Secklers' guest room that summer.

But as DART progressed, the vision changed. For the first two years, it was a virtual company, pursuing a few deals here and there. But by summer 2012, things still weren't moving fast enough—not for the Secklers, not for Williams, not for Charley. So Williams became chairman and CEO and added a veteran executive team filled with his former industry colleagues—including former CFO Cabot Brown (MBA 1987)—all of them bringing not only two or three decades of experience in drug development, fundraising, and dealmaking but also a discernible dissatisfaction with the state of the industry. Because, Williams's thinking went, the next step for DART was to implement a whole new model for drug development—one where a biotech company is funded by investors but driven by the very people benefiting from the outcomes: the patients.

Making It Personal

Gene Williams joins a number of HBS alums who are leading personal crusades against rare diseases.

Kathy Giusti (MBA 1985) cofounded the Multiple Myeloma Research Foundation soon after being diagnosed with the blood cancer in 1996. Since then, MMRF has raised over $225 million, started 45 drug trials, and mapped the myeloma genome.

Diagnosed with ALS (Lou Gehrig's disease) while at HBS, Avi Kremer (MBA 2007) and several of his classmates established Prize4Life, which offers awards to incentivize ALS research. Last year, the nonprofit also unveiled a revolutionary open-source ALS clinical trials database in an effort to spur further developments.

John Crowley's (MBA 1997) quest to conquer Pompe disease began when his son and daughter were diagnosed with the rare, often fatal neuromuscular disorder in 1998. He helped push the development of the first-ever treatment for Pompe, approved by the FDA in 2006; his children are now in high school.

The Joey Fund—started by Joe O'Donnell (MBA 1971) in 1986 in memory of his son, a victim of cystic fibrosis—has raised more than $56 million to support both patients and research. Last year, a longtime partnership with Vertex produced the first-ever FDA-approved cystic fibrosis treatment.

Williams got into pharma by chance. After working in investment banking before and after HBS, he took a job at the consulting firm Corporate Decisions (now Oliver Wyman). One of his first clients was launching a drug that would help prevent organ transplant rejection. While growing up in Michigan, Williams witnessed the satisfaction that his father and grandfather, both primary care physicians, got from helping others heal. This was his chance to feel that, too. "It was really an exposure to the kind of impact you could have in this business," notes Williams, sitting in a conference room at DART's Cambridge office.

After several years in consulting and a few years launching start-ups, Williams spent eight years at Genzyme, managing its rare disease portfolio, leaving in 2006 to take on a number of smaller pharma gigs. "I was doing four or five different things, pursuing what a friend of mine called a 'collage career'—never a boss, never a full-time job—which is really cool."

And he would have been happy doing that for a while, but then Tracy Seckler called, and he saw a chance to heal again. "I said, 'Look, if I don't throw myself into this, somebody is going to have to, because it has to be addressed,' " says Williams. Reserved and soft-spoken, Williams grows animated when he talks about DART, his arms flying out in front of him, accentuating his points.

The way he sees it, Big Pharma is against a wall. The classic blockbuster profit model forces companies to be hyper-focused on developing the next Lipitor or Levitra, creating a constant drain on financial and human resources. And companies are running out of big ideas and facing gaps in their revenue thanks to patent expirations, leaving investors pressured and skittish. Perhaps rightfully so: According to the trade group Pharmaceutical Research and Manufacturers of America (PhRMA), only one of 5,000 to 10,000 experimental compounds make it to FDA approval, and just 2 of the 10 that get that approval produce enough revenue to exceed the cost of their development, which averages more than a billion dollars. All told, the process takes about 10 to 15 years. "I think we're all frustrated, we're all disappointed," explains PhRMA's EVP of scientific and regulatory affairs Bill Chin, former executive dean for research at Harvard Medical School. And while he sees more drugs in the clinical development pipeline, the time and money the trials cost companies hurts research—a lack of which is the industry's core problem, he says: "We simply don't understand what causes most diseases."

It all adds up to an environment that leaves rare diseases—especially those like DMD, which require a cocktail of treatments rather than a single "magic bullet"—in an especially tough spot.

DART, then, is the blueprint for a new model: philanthropic, patient-led organizations—whose agility, narrow focus, and autonomy increase efficiency—working in partnership with financial investors who are attracted to this more efficient process. The big companies, notes Williams, are too big; innovation, he says—particularly these kinds of radically reengineered and modified models—is the province of smaller companies. And groups like the Secklers have the passion but lack both the big money and the industry know-how to move things forward. "I think that engaged, capable patients who also bring fundraising capabilities to the table, working with industry professionals, are going to drive a lot of the innovation we will see over the next 10 to 15 years," says Williams.

"It's a very, very powerful concept," says drug development expert Ken Getz, director of sponsored research and an associate professor at the Tufts University School of Medicine. Getz notes that even Big Pharma has started to recognize the importance of engaging patients as partners in the drug development process. But DART is the first he's seen employ this kind of model. "DART is a pioneer. It is a case study for larger companies to follow."

"It's almost like somebody has the ability to build the Panama Canal or a highway through the jungle—whatever it is. If that superhighway gets laid down, then lifesaving therapies are going to start. The investors can pay for the cars and the gas. We can drive the cars really fast."—Gene Williams

Photo by Mark Ostow

And Williams is more than happy to provide a model. "It's almost like somebody has the ability to build the Panama Canal or a highway through the jungle—whatever it is," he says. His hands are in front of him, drawing a road. "If that superhighway gets laid down, then lifesaving therapies are going to start. The investors can pay for the cars and the gas. We can drive the cars really fast."

Charley took his first pills in July, part of an initial easing on to the drug to make sure he could tolerate it. The night of the first dose, he asked for sushi—not a typical choice for someone feeling nauseated. Halfway into a third order of edamame, he froze. "Oh my God," pointing to a maggot in the food, "I'm going to throw up, and they're going to think it was from the medicine," recalls Tracy with a laugh. "He was so worried about screwing up the data."

Charley is currently one of 30 boys and young men with DMD in the trial, which is taking place at five sites across the country. "It was 28 months from the time we acquired the asset to the time the first child swallowed that pill," Tracy says. "That's just unheard of." If all goes well, the next move could be trials for FDA approval. And HT-100 is just one of the drugs that DART is involved in. It is funding a cardiac drug for DMD, on the verge of starting a human trial for a muscle-strengthening agent, and eyeing a few other compounds owned by struggling biotechs. Williams usually calls Tracy once or twice a day, with about a dozen emails back and forth daily. Things are moving.

Long term, the Secklers see stem cell or gene replacement therapy wiping out the disease in 15 years. Short term, they want to keep pushing to make sure that Charley and other kids with DMD can make it there—and have some semblance of a normal life. While Benjy describes his middle child as energetic—"You'd be hard-pressed to know he has such an active disease," he notes—Charley's daily steroid treatments have stunted his growth. "HT-100 may or may not prove to be tolerable, and it may or may not prove to be efficacious," says Tracy. "But even if it doesn't, I feel that what we've done has bushwhacked a path."

For Williams, he sees the potential for impact writ large. He offers numbers: About 5 million kids in the United States alone suffer from rare diseases that severely impact their lives. "And of those 5 million, a fraction, maybe 10 percent, have a disease where a magic bullet could be the answer." So that's more than 4 million kids in the United States—with double that in Europe, he says—who are being forgotten. There is much healing to be done.